Silibinin (INN), also known as silybin (both from Silybum, the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silicristin, silidianin, and others. Silibinin itself is mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio.[1] The mixture exhibits a number of pharmacological effects, particularly in the liver, and there is some clinical evidence for the use of silibinin as a supportive element in alcoholic and child grade 'A' liver cirrhosis.[2]

Contents

Poor water solubility and bioavailability of silymarin led to the development of enhanced formulations. Silipide (trade name Siliphos), a complex of silymarin and phosphatidylcholine (lecithin), is about 10 times more bioavailable than silymarin.[3] An earlier study had concluded Siliphos to have 4.6 fold higher bioavailability.[4] It has been also reported that silymarin inclusion complex with β-cyclodextrin is much more soluble than silymarin itself.[5] There have also been prepared glycosides of silybin, which show better water solubility and even stronger hepatoprotective effect.[6]

Silymarin, as other flavonoids, has been shown to inhibit P-glycoprotein-mediated cellular efflux.[7] The modulation of P-glycoprotein activity may result in altered absorption and bioavailability of drugs that are P-glycoprotein substrates. It has been reported that silymarin inhibits cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.[8]

A phase I clinical trial in humans with prostate cancer designed to study the effects of high dose silibinin found 13 grams daily to be well tolerated in patients with advanced prostate cancer with asymptomatic liver toxicity (hyperbilirubinemia and elevation of alanine aminotransferase) being the most commonly seen adverse event.[9]

Silymarin is also devoid of embryotoxic potential in animal models.[10][11]

Silibinin is available as drug (Legalon® SIL (Madaus) (D, CH, A) and Silimarit® (Bionorica), a Silymarin product) in some EU countries and used in the treatment of toxic liver damage (e.g. IV treatment in case of death cap poisoning); as adjunctive therapy in chronic hepatitis and cirrhosis. See also Silybum marianum#Medicinal use

Silibinin is under investigation to see whether it may have a role in cancer treatment (e.g. due to its inhibition of STAT3 signalling).[12]

Silibinin also has a number of potential mechanisms that could benefit the skin. These include chemoprotective effects from environmental toxins, anti-inflammatory effects, protection from UV induced photocarcinogenesis, protection from sunburn, protection from UVB-induced epidermal hyperplasia, and DNA repair for UV induced DNA damage (double strand breaks).[13]